Repare Therapeutics has revealed initial results from its ongoing Phase l/ll TRESR and Phase lb/ll ATTACC trials of combination therapies for solid tumours.

The TRESR trial has been designed to assess camonsertib in combination with talazoparib poly (ADP-ribose) polymerase inhibitor (PARPi) for the treatment of various types of tumours.

The initial TRESR trial included 107 patients, of whom 90 were evaluable for efficacy treated at least 13 weeks before the data cut-off of 27 February 2023.

ATTACC is evaluating camonsertib plus two PARPis, niraparib or olaparib, to treat patients with advanced solid tumours.

The newly presented data showed that the camonsertib combination led to durable clinical benefit across tumour types and various genomic alterations, irrespective of PARPi choices and presence of platinum resistance.

For all patients, overall clinical benefit rate (CBR) was reported to be 48%.

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Patients with platinum-resistant tumours had 12% overall response rate (ORR) and 49% CBR.

In addition, patients with advanced ovarian cancer had 32% ORR and 58% CBR. The median progression-free survival reported in these patients was around seven months, with more than 16 weeks of treatment and ongoing in nine patients.

The initial data also demonstrated that early circulating tumour DNA molecular responses in 66% of evaluable patients validates anti-tumour activity of low dose, intermittent PARPi + ATRi therapy.

Molecular responses were reported in patients with prior exposure to PARPi and platinum resistance.

The camonsertib combinations were found to be well tolerated.

Dose limiting toxicity in 68 patients who received the proposed combination doses were associated with only myelotoxicity.

No prophylactic growth factors were needed when given the PARPis at evaluated doses.

Repare chief medical officer Maria Koehler said: “We see promise in the camonsertib-PARPi combinations when administered concomitantly, at low doses across tumour types, especially in recurrent ovarian cancer given that nearly all had recurred after prior PARPi treatment.

“We are particularly encouraged by the depth of response and duration of treatment.

“Dose optimisation to refine the combinatorial dose in additional tumour-specific expansions beyond ovarian within our ATTACC study, is ongoing as part of our collaboration with Roche.”